To address the constrains imposed by insufficient hydrogen peroxide (H2O2) and high glutathione (GSH) expression in tumor cells on the efficacy of chemodynamic therapy (CDT), zeolitic imidazolate framework-8 (ZIF-8) loaded with disulfiram (DSF) and 3-amino-1,2,4-triazole (3-AT) was synthesized via a one-pot approach. Subsequently, hyaluronic acid (HA)-modified cupric peroxide (CuO2) was in-situ grown on its surface through biomineralization to construct a multifunctional copper-based nanozyme ADZCH (3-AT/DSF@ZIF-8@CuO2-HA). This nanoplatform disrupts the intratumoral H2O2 homeostasis, depletes GSH, and synchronously delivers DSF and Cu2+ via cascade catalysis, thereby enhancing CDT and sensitizing tumors to DSF-based chemotherapy. The results of physicochemical characterization indicated that ADZCH presented a uniform core-shell structure with favorable dispersibility. Its particle size and Zeta potential were 196.5 nm and −19.5 mV, respectively. It possessed a microporous structure with a specific surface area of 81.8600 m2/g, and demonstrated efficient loading capacity for DSF and 3-AT, achieving drug loading efficiencies of 5.91% and 45.07%, respectively. Moreover, ADZCH can continuously and slowly release drugs in an acidic environment and maintain good stability under diverse physiological conditions. In vitro functional assays verified that ADZCH catalytically generated H2O2 and hydroxyl radicals while concurrently depleting GSH in a concentration- and incubation time-dependent manner. Cellular uptake experiments showed that HA modification significantly improved the uptake of nanoparticles by 4T1 cells. Cytotoxicity tests showed that 80 μg/mL ADZCH had a significant cytotoxic effect on 4T1 cells but no significant toxicity on L929 cells. DCFH-DA probe detection indicated that ADZCH could significantly induce intracellular reactive oxygen species (ROS) generation, thereby enhancing CDT efficacy. Live/dead staining experiments showed that ADZCH efficiently induced apoptosis, with the proportion of dead cells reaching 94.74%, demonstrating its promising potential for anti-tumor applications.This study provides new research ideas and experimental basis for overcoming the tumor microenvironment barrier and enhancing the anti-tumor effect of CDT combined with chemotherapy.

This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*

The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

BACKGROUND AND OBJECTIVE: Patients with glioma experience a high symptom burden and have diverse palliative care needs. However, the assessment scales used in palliative care remain non-standardized and highly heterogeneous. To evaluate the application patterns of the current scales used in palliative care for glioma, we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care. METHODS: We conducted a systematic search of five databases including PubMed, Web of Science, Medline, EMBASE, and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care. We extracted data on scale characteristics, domains, frequency, and psychometric properties. Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools. RESULTS: Of the 3,405 records initially identified, 72 studies were included. These studies contained 75 distinct scales that were used 193 times. Mood (21.7%), quality of life (24.4%), and supportive care needs (5.2%) assessments were the most frequently assessed items, exceeding half of all scale applications. Among the various assessment dimensions, the Distress Thermometer (DT) was the most frequently used tool for assessing mood, while the Short Form-36 Health Survey Questionnaire (SF-36) was the most frequently used tool for assessing quality of life. The Mini Mental Status Examination (MMSE) was the most common tool for cognitive assessment. Performance status (5.2%) and social support (6.8%) were underrepresented. Only three brain tumor-specific scales were identified. Caregiver-focused scales were limited and predominantly burden-oriented. CONCLUSIONS: There are significant heterogeneity, domain imbalances, and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care. The scale selected for use should be comprehensive and user-friendly.
Humans ; Glioma/psychology* ; Palliative Care/methods* ; Quality of Life ; Psychometrics ; Brain Neoplasms/psychology*

The connection between tendons and bones is called the tendon bone connection. With the continuous improvement of national sports awareness, excessive exercises and the related intensity are prone to damage the tendon bone connection. Tendon bone healing is a complex repair and healing process involving multiple factors, and good tendon bone healing is a prerequisite for its physiological function. The complexity of tendon bone structure also poses great challenges to the repair of tendon bone injuries. In recent years, researches have found that stem cells, growth factors, macrophages, and other factors are closely related to the healing process of tendon bone injuries, among which macrophages play an important role in the healing process. The authors reviewed relevant research literature in recent years and summarized the role of macrophages in tendon bone healing, in order to provide new ideas and directions for treatment strategies to promote tendon bone healing.
Humans ; Macrophages/metabolism* ; Wound Healing ; Animals ; Tendons/physiology* ; Bone and Bones/injuries* ; Tendon Injuries

Accurate analysis of metal nanoparticles(MNPs)in sediments is a prerequisite for assessing the ecological risks of MNPs in aquatic environmental sediments.In this study,an analytical method for quantitative detection of concentration and particle size distribution of silver-containing nanoparticles(Ag-NPs),zinc-containing nanoparticles(Zn-NPs),cerium-containing nanoparticles(Ce-NPs),and titanium-containing nanoparticles(Ti-NPs)in sediments was established based on ultrasonic extraction-single particle inductively coupled plasma mass spectrometry(SP-ICP-MS).The effects of sample preparation conditions such as extraction solvent type,solid-liquid ratio,ultrasonic time,and settling time on the recovery of MNPs were investigated.The results showed that the extraction of MNPs from sediment by distilled water could effectively eliminate the high background signal interference introduced by the extractant under the conditions of solid-liquid ratio of 1∶400(g∶mL),ultrasonic extraction time of 1 h and settling time of 3 h.The detection limits for particle size of Ag-NPs,Zn-NPs,Ce-NPs and Ti-NPs in sediments were 31,35,26 and 85 nm,respectively,while the detection limits of particle concentrations were 1.21×104,1.90×104,5.26×107 and 1.48×107 particles/g,respectively.The spiking recoveries of Ag-NPs,Zn-NPs,Ce-NPs and Ti-NPs in sediments were 62.1％-108.7％,with relative standard deviations below 10％.This method could rapidly,accurately and simultaneously determine the concentration and particle size distribution of various MNPs in sediments,and was successfully applied to analysis of Ag-NPs,Zn-NPs,Ce-NPs,and Ti-NPs in authentic marine sediments.

Objective:To evaluate the clinical efficacy and prognosis of mechanical lithotripsy, laser lithotripsy under direct peroral cholangioscopy, and their combination in the treatment of difficult common bile duct (CBD) stones.Methods:Clinical data of 345 patients with difficult CBD stones treated at the Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, between January 2020 and December 2024 were retrospectively analyzed, including 176 males and 169 females, aged (71.2±14.2) years. Patients were categorized into three groups based on the lithotripsy technique used: mechanical lithotripsy group ( n=275), laser lithotripsy group under direct peroral cholangioscopy ( n=34), and combined lithotripsy group ( n=35). Operative time, hospitalization costs, stone clearance rate, and postoperative complications were recorded. Follow-ups were conducted through outpatient visits and telephone reviews to monitor stone recurrence. Propensity score matching (PSM) at a 1: 3 nearest-neighbor ratio with a caliper of 0.02 was performed, using lithotripsy method as the dependent variable, and age, sex, stone size, and bile duct diameter as independent variables, resulting in well-balanced mechanical and laser lithotripsy groups. Kaplan-Meier survival analysis was used to assess recurrence-free survival, with comparisons performed using the log-rank test. Results:Before PSM, there were significant differences in age, sex, stone length, and bile duct diameter between the groups (all P<0.05). After PSM, 40 patients were included in the mechanical lithotripsy group, 34 in the laser group, and 35 in the combined group, with no significant differences in baseline or preoperative clinical characteristics (all P>0.05). The combined group had a significantly longer operative time compared to the mechanical group [71.0 (66.0, 92.0) min vs. 50.5 (40.4, 56.5) min, Z=-5.02, P<0.001] and the laser group [71.0 (66.0, 92.0) min vs. 53.0 (26.5, 73.5) min, Z=-2.61, P=0.001]. The laser group also had a longer operative time than the mechanical group [53.0 (26.5, 73.5) min vs. 50.5 (40.4, 56.5) min, Z=-2.27, P=0.023]. Hospitalization costs were significantly higher in the combined group compared to the mechanical group [43 000(33 000, 50 000) yuan vs. 30 000(26 000, 37 000) yuan; Z=-3.43, P<0.001]. The single-session stone clearance rates were 80.0% (32/40) for the mechanical group, 85.3% (29/34) for the laser group, and 62.9% (22/35) for the combined group. Postoperative complication rates were 20.0% (8/40), 11.7% (4/34), and 11.4% (4/35), respectively, with no statistically significant differences among the three groups (all P>0.05). There were also no significant differences in cumulative recurrence-free survival among the groups ( χ2=0.06, P=0.970). Conclusions:For endoscopic management of difficult CBD stones, combined lithotripsy is associated with longer operative time and higher hospitalization costs compared to mechanical and laser lithotripsy alone. Laser lithotripsy also requires more operative time than mechanical lithotripsy. However, the three lithotripsy strategies show no significant differences in postoperative complications or cumulative recurrence-free survival.

Objective To observe the value of artificial intelligence iterative reconstruction(AIIR)for improving image quality of 80 kVp low-dose CT enterography(CTE)for Crohn disease(CD).Methods Totally 59 patients with CD who underwent 80 kVp low-dose CTE were retrospectively enrolled,and CTE images were reconstructed with hybrid iterative reconstruction(HIR)(HIR group)and AIIR(AIIR group),respectively.Then subjective and objective scores of image quality were evaluated and compared between groups,and the value of AIIR was analyzed.Results Compared with HIR group,AIIR group clearly displayed the intestinal wall,intestinal lumen,mesenteric vessels and peri-intestinal soft tissue,and displayed typical CD signs more obviously,with higher subjective scores of imaging quality(all P＜0.001).The standard deviation(SD)was lower,while signal-to-noise ratio(SNR)of intestinal walls without disease,SNR and contrast-to-noise ratio(CNR)of diseased intestinal walls in AIIR group were all higher than those in HIR group(all P＜0.001).The effective dose of 80 kVp CTE examination was(2.82±0.54)mSv.Conclusion AIIR was helpful for improving image quality of 80 kVp low-dose CTE for CD.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.